A Randomized Study of Sativex on Cognitive Function and Mood: Multiple Sclerosis Patients

NCT01964547 | Completed Phase 4 Results

• 1 other identifier: GWMS1137
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 1

Brief Summary

A study to compare the change in cognitive performance and psychological status of patients with spasticity due to Multiple Sclerosis when treated with Sativex or placebo, added to existing anti-spasticity therapy over a period of 48 weeks. Secondary objectives were to evaluate the effect of Sativex on mood and spasticity and to assess the safety and tolerability of Sativex.

Conditions

Multiple Sclerosis; Spasticity

Keywords

Cognition; Mood

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to the End of Treatment in Paced Auditory Serial Addition Test (PASAT) Total Score.

  The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Stimulus presentation rates were adapted for use with multiple sclerosis patients. The PASAT is presented on audio compact disk to control the rate of stimulus presentation. Single digits are presented either every 3 seconds (PASAT 1) or every 2 seconds (PASAT 2), and the patient must add each new digit to the one immediately prior to it. The test score is the sum of the total number of correct sums given (out of 60 possible) in each trial. An increase in score indicates an improvement in condition.

  0-48 weeks

Secondary Outcomes (9)

• Change From Baseline to the End of Treatment in Beck Depression Inventory-II (BDI-II) Total Score.

  0-48 weeks

• Subject Global Impression of Change (SGIC) in the Severity of Their Spasticity at the End of Treatment.

  0-48 weeks

• Caregiver's Global Impression of Change (CGIC) in the Severity of the Patient's Spasticity at the End of Treatment.

  0-48 weeks

• Physician's Global Impression of Change (PGIC) in the Severity of the Patient's Spasticity at the End of Treatment.

  0-48 weeks

• Change From Baseline to End of Treatment in Modified Ashworth Scale Total Score.

  0-48 weeks

Study Arms (2)

Sativex

ACTIVE COMPARATOR

Contains delta-9-tetrahydrocannabinol (THC), 27 mg/mL:cannabidiol (CBD), 25 mg/mL, in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Each actuation delivers THC 2.7 mg and CBD 2.5 mg. Dose: 100 µL oromucosal spray to be administered up to a maximum of 12 sprays per day. There was an initial dose-titration period during which patients gradually increased their dose of study drug according to individual response and tolerability.

Drug: Sativex

Placebo

PLACEBO COMPARATOR

Oromucosal spray, containing ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring and colourings FD\&C Yellow No.5 (E102 tartrazine) (0.0260%), FD\&C Yellow No.6 (E110 sunset yellow) (0.0038%), FD\&C Red No. 40 (E129 Allura red AC) (0.00330%) and FD\&C Blue No.1 (E133 Brilliant blue FCF) (0.00058%). Dose: 100 µL oromucosal spray to be administered up to a maximum of 12 sprays per day. There was an initial dose-titration period during which patients gradually increased their dose of study drug according to individual response and tolerability.

Drug: Placebo

Interventions

Sativex DRUG

Patients self-administered their allocated randomized treatment on an outpatient basis, up to a maximum of 12 sprays to the oral mucosa per day (following an initial titration period).

Also known as: Nabiximols, GWP42001, THC/CBD spray

Sativex

Placebo DRUG

Patients self-administered their allocated randomized treatment on an outpatient basis, up to a maximum of 12 sprays to the oral mucosa per day (following an initial titration period).

Also known as: Placebo control

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is willing and able to give informed consent for participation in the study.
• Patient is aged 18 years or above.
• Diagnosed with any disease sub-type of multiple sclerosis.
• Diagnosed with symptomatic spasticity due to multiple sclerosis.
• Patient has at least moderate spasticity in the opinion of the investigator.
• Patient fulfils at least one of the two criteria below. Subject must be either:
• Currently established on a regular dose of anti-spasticity therapy, or
• Previously tried and failed anti-spasticity therapy.
• Stable medication regimen for at least four weeks prior to study entry, for all medications which may have an effect on spasticity and/or cognition.
• If the patient is taking disease modifying medication this must be at a stable dose for three months prior to the initial visit.
• Willing and able to comply with all study requirements.
• Willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable.
• Willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study.

You may not qualify if:

• Any history or immediate family of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
• Any concomitant disease or disorder (such as poorly controlled epilepsy or seizures) that may influence the patient's level of cognition or mood.
• Currently using or has used cannabis or cannabinoid-based medications within 30 days of study entry and unwilling to abstain for the duration of the study.
• Any known or suspected history of a diagnosed dependence disorder, current heavy alcohol consumption (more than 60g of pure alcohol per day for men, and more than 40g of pure alcohol per day for women), current use of an illicit drug or current non-prescribed use of any prescription drug.
• Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal products.
• Female patients of child bearing potential and male subjects whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective contraception during the study and for three months thereafter.
• Female patient who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.
• Patients who have received an investigational medicinal product within the 12 weeks prior to the initial visit.
• Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study may influence the result of the study, or the patient's ability to participate in the study.
• Following a physical examination, the patient has any abnormalities that, in the opinion of the investigator would prevent the patient from safe participation in the study.
• Previously randomised to this study.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (1)

MS Centre, Charles University

Prague, 128 08, Czechia

Location

Related Publications (2)

• Abstracts of ECTRIMS (Congress of the European Committee for Treatment and Research in Multiple Sclerosis) 2013. October 2-5, 2013. Copenhagen, Denmark. Mult Scler. 2013 Oct;19(11 Suppl):8-597. No abstract available.

  PMID: 24151639 RESULT

• Bosnjak Kuharic D, Markovic D, Brkovic T, Jeric Kegalj M, Rubic Z, Vuica Vukasovic A, Jeroncic A, Puljak L. Cannabinoids for the treatment of dementia. Cochrane Database Syst Rev. 2021 Sep 17;9(9):CD012820. doi: 10.1002/14651858.CD012820.pub2.

  PMID: 34532852 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Muscle Spasticity

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Mr Richard Potts, Clinical Operations Director
• Organization: GW Pharma Ltd.

rp@gwpharm.com

0044 1223 266800

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2013
• First Posted: October 17, 2013
• Study Start: January 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: January 12, 2023
• Results First Posted: May 2, 2014

Record last verified: 2022-12

Locations

CZ (1)